TY - JOUR
T1 - Effects of Haplotype Matching on Outcomes after Adult Single-Cord Blood Transplantation
AU - HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation
AU - Kanda, Junya
AU - Kawase, Takakazu
AU - Tanaka, Hidenori
AU - Kojima, Hiroto
AU - Morishima, Yasuo
AU - Uchida, Naoyuki
AU - Nagafuji, Koji
AU - Matsuhashi, Yoshiko
AU - Ohta, Takanori
AU - Onizuka, Makoto
AU - Sakura, Toru
AU - Takahashi, Satoshi
AU - Miyakoshi, Shigesaburo
AU - Kobayashi, Hikaru
AU - Eto, Tetsuya
AU - Tanaka, Junji
AU - Ichinohe, Tatsuo
AU - Atsuta, Yoshiko
AU - Morishima, Satoko
N1 - Funding Information:
The authors are indebted to all physicians and data managers who contributed valuable transplant data to the Japan Society for Hematopoietic Cell Transplantation (JSHCT). The authors also thank the members of the data management committee of the JSHCT for their assistance. Financial disclosure: This work was supported in part by the Takeda Science Foundation (to J.K.) and the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development, AMED (to Y.A. and J.K.). Conflict of interest statement: J.T.: Research funding, Bristol-Myers Squibb; honoraria, Novartis Pharma, Bristol-Myers Squibb, Otsuka, Pfizer. T.I.: Research funding, Astellas Pharma, Chugai Pharmaceutical Co. CSL Behring, Eisai Co. Kyowa Hakko Kirin Co. Ono Pharmaceutical Co. Pfizer, Nippon Shinyaku Co. MSD, Otsuka Pharmaceutical Co. Repertoire Genesis Inc. Sumitomo Dainippon Pharma Co. Taiho Pharmaceutical Co. Takeda Pharmaceutical Co. Zenyaku Kogyo Co.; honoraria, Alexion Pharmaceuticals, Bristol-Myers Squibb, Celgene, JCR Pharmaceuticals, Janssen Pharmaceutical K.K. Mundipharma, Novartis. Authorship statement: J.K. designed the research, organized the project, performed the statistical analysis, and analyzed the data. T.K. H.T. H.K.Y.M. and S.M. analyzed and interpreted the data. N.U. K.N. Y.M. T.O. M.O. T.K. S.T. S.M. H.K. T.E. J.T. T.I. and Y.A. gathered and organized the data. J.K. wrote the first draft, and all other authors contributed to the final version. Financial disclosure: See Acknowledgments on page 517.
Funding Information:
The authors are indebted to all physicians and data managers who contributed valuable transplant data to the Japan Society for Hematopoietic Cell Transplantation (JSHCT). The authors also thank the members of the data management committee of the JSHCT for their assistance. Financial disclosure: This work was supported in part by the Takeda Science Foundation (to J.K.) and the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development, AMED (to Y.A. and J.K.). Conflict of interest statement: J.T.: Research funding, Bristol-Myers Squibb; honoraria, Novartis Pharma, Bristol-Myers Squibb, Otsuka, Pfizer. T.I.: Research funding, Astellas Pharma, Chugai Pharmaceutical Co., CSL Behring, Eisai Co., Kyowa Hakko Kirin Co., Ono Pharmaceutical Co., Pfizer, Nippon Shinyaku Co., MSD, Otsuka Pharmaceutical Co., Repertoire Genesis Inc., Sumitomo Dainippon Pharma Co., Taiho Pharmaceutical Co., Takeda Pharmaceutical Co., Zenyaku Kogyo Co.; honoraria, Alexion Pharmaceuticals, Bristol-Myers Squibb, Celgene, JCR Pharmaceuticals, Janssen Pharmaceutical K.K., Mundipharma, Novartis. Authorship statement: J.K. designed the research, organized the project, performed the statistical analysis, and analyzed the data. T.K., H.T., H.K.,Y.M., and S.M. analyzed and interpreted the data. N.U., K.N., Y.M., T.O., M.O., T.K., S.T., S.M., H.K., T.E., J.T., T.I., and Y.A. gathered and organized the data. J.K. wrote the first draft, and all other authors contributed to the final version.
Publisher Copyright:
© 2019 American Society for Transplantation and Cellular Therapy
PY - 2020/3
Y1 - 2020/3
N2 - It remains unclear whether the HLA haplotype of unrelated cord blood (UCB) should be matched to that of the patient in single UCB transplantation. Thus, using data from a Japanese registry, we analyzed the effect of haplotype matching on outcomes. Patients with hematologic diseases aged 16 years or older who had undergone their first transplant were included (N = 1347). The effects of haplotype matching and high-frequency HLA haplotype on outcomes were analyzed. Median patient age was 55 years. The cumulative incidences of neutrophil engraftment among groups with 0, 1, and 2 HLA haplotype matches were 79%, 82%, and 88%, respectively (P = .008). In a multivariate analysis, the group with 0 haplotype matches was marginally associated with worse neutrophil engraftment (P = .087) and significantly associated with platelet engraftment (P = .044) compared with the group with 1 haplotype match. Two-haplotype matches were associated with a higher risk of relapse. In the group with 1 haplotype match, the top 3 shared haplotypes were "A*24:02-B*52:01-C*12:02-DRB1*15:02" (HP-P1), "A*33:03-B*44:03-C*14:03-DRB1*13:02" (HP-P2), and "A*24:02-B*07:02-C*07:02-DRB1*01:01" (HP-P3). The presence of HP-P2 but not HP-P1 or HP-P3 was associated with a decreased risk of grades II to IV acute graft-versus-host disease (hazard ratio,. 56; P = .001) but an increased risk of relapse (hazard ratio, 1.35; P = .045). HLA haplotype matching might be considered to improve engraftment. Two-haplotype matches should be avoided if the relapse risk is high. The haplotype itself may have an effect on the risk of acute graft-versus-host disease and relapse.
AB - It remains unclear whether the HLA haplotype of unrelated cord blood (UCB) should be matched to that of the patient in single UCB transplantation. Thus, using data from a Japanese registry, we analyzed the effect of haplotype matching on outcomes. Patients with hematologic diseases aged 16 years or older who had undergone their first transplant were included (N = 1347). The effects of haplotype matching and high-frequency HLA haplotype on outcomes were analyzed. Median patient age was 55 years. The cumulative incidences of neutrophil engraftment among groups with 0, 1, and 2 HLA haplotype matches were 79%, 82%, and 88%, respectively (P = .008). In a multivariate analysis, the group with 0 haplotype matches was marginally associated with worse neutrophil engraftment (P = .087) and significantly associated with platelet engraftment (P = .044) compared with the group with 1 haplotype match. Two-haplotype matches were associated with a higher risk of relapse. In the group with 1 haplotype match, the top 3 shared haplotypes were "A*24:02-B*52:01-C*12:02-DRB1*15:02" (HP-P1), "A*33:03-B*44:03-C*14:03-DRB1*13:02" (HP-P2), and "A*24:02-B*07:02-C*07:02-DRB1*01:01" (HP-P3). The presence of HP-P2 but not HP-P1 or HP-P3 was associated with a decreased risk of grades II to IV acute graft-versus-host disease (hazard ratio,. 56; P = .001) but an increased risk of relapse (hazard ratio, 1.35; P = .045). HLA haplotype matching might be considered to improve engraftment. Two-haplotype matches should be avoided if the relapse risk is high. The haplotype itself may have an effect on the risk of acute graft-versus-host disease and relapse.
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U2 - 10.1016/j.bbmt.2019.09.035
DO - 10.1016/j.bbmt.2019.09.035
M3 - Article
C2 - 31605821
AN - SCOPUS:85075415719
SN - 1083-8791
VL - 26
SP - 509
EP - 518
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 3
ER -